Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections

• Type: Article in International Scientific Journal
• Date: 2023

Authors

Ramoa, AM (Author) Other; Campos, F (Author) Other; Moreira, L (Author) Other; Teixeira, C (Author) Other; Leiro, V (Author) Other; Paula Gomes (Author) FCUP; das Neves, J (Author) Other; Martins, MCL (Author) Other; Monteiro, C (Author) Other

Journal

Title: Biomaterials Science

Vol. 11

Pages: 499-508

ISSN: 2047-4830

Publisher: Royal Society of Chemistry

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00X-J79

DOI: 10.1039/d2bm01127a

Abstract (EN): Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(d,l-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4-20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 +/- 1.8 mV) and AMP quantification (326 mu g mL(-1), corresponding to 16.3 mu g of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8-16 mu g mL(-1) against Pseudomonas aeruginosa, and 16-32 mu g mL(-1) against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1-2 h to 15 min for P. aeruginosa and from 6-8 h to 0.5-1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10